Research Interests:The treatment of head and neck cancer has constituted both my principal clinical focus and the framework for my research efforts since my arrival at Duke in 1987. I led an in house randomized trial which was one of the first to demonstrate that concurrent chemoradiation was more efficacious than radiotherapy alone for locally advanced head and neck cancer. Two aspects of this trial were unique: a) the RT alone control arm utilized accelerated hyperfractionation with doses >70 Gy many years before other clinical trials confirmed the validity of this type of fractionation as optimal single modality treatment, and b) the more effective chemoradiation arm employed lower total RT doses than the control arm. Subsequent analyses of this trial showed that loss of heterozygosity (LOH) of the M6P-IGF2R tumor suppressor gene was associated with a greater risk of recurrence after RT alone whereas patients without LOH who received RT alone recurred no more frequently than patients receiving chemoradiation. These findings suggest that this parameter could identify a favorable subset of patients with advanced disease who could be adequately treated with RT alone thus avoiding the added morbidity of chemoradiation.

Reduction of treatment induced morbidity has been a major interest of mine. I served as the principal investigator of the pivotal randomized trial of amifostine in head and neck cancer. This study established proof of priniciple for the feasibility of pharmacologic radioprotection. The FDA approved this drug for protection against radiation induced xerostomia based on this trial. Presently, I am involved in preclinical and clinical studies that are evaluating the potential role of keratinocyte growth factor for protection against radiation induced mucositis and pneumonitis.

I have a long term commitment to the study of tumor physiology and biology in my patients. This work has demonstrated the association between tumor hypoxia and local-regional failure in head and neck cancer and distant failure in soft-tissue sarcoma. It has also shown that elevated tumor lactate concentrations at diagnosis in patients with head and neck cancer are associated with an increased risk of metastatic failure after treatment. Presently, I am serving as co-Principal Investigator of a multinational randomized trial that is testing the benefit adding the hypoxic cell cytotoxin, tirapazamine, to concurrent chemoradiation in advanced head and neck cancer. I have also just initiated an in house pilot study that will investigate the clinical efficacy of combined EGFR and VEGF blockade administered simultaneously with a regimen of hyperfractionated irradiation and concurrent cisplatin in head and neck cancer.

The translational nature of my work has allowed me to become proficient in clinical care, the design and execution of clinical trials, and the conduct of laboratory investigation. It provides me with ideal opportunities to try to improve the therapeutic index of the treatments that we offer to our patients.